High‐glucose concentration aggravates TNF‐alpha‐induced cell viability reduction in human CD146‐positive periodontal ligament cells via TNFR‐1 gene demethylation

2020 ◽  
Vol 44 (12) ◽  
pp. 2383-2394
Author(s):  
Haoyuan Luo ◽  
Wenjun Zhu ◽  
Weiyan Mo ◽  
Min Liang
2020 ◽  
Vol 8 (2) ◽  
pp. e001458
Author(s):  
Amal Ashour ◽  
Mingzhan Xue ◽  
Maryam Al-Motawa ◽  
Paul J Thornalley ◽  
Naila Rabbani

IntroductionPatients with diabetes have increased risk of periodontal disease, with increased risk of weakening of periodontal ligament and tooth loss. Periodontal ligament is produced and maintained by periodontal ligament fibroblasts (PDLFs). We hypothesized that metabolic dysfunction of PDLFs in hyperglycemia produces an accumulation of the reactive glycating agent, methylglyoxal (MG), leading to increased formation of the major advanced glycation endproduct, MG-H1 and PDLF dysfunction. The aim of this study was to assess if there is dicarbonyl stress and functional impairment of human PDLFs in primary culture in high glucose concentration—a model of hyperglycemia, to characterize the metabolic drivers of it and explore remedial intervention by the glyoxalase 1 inducer dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP).Research design and methodsHuman PDLFs were incubated in low and high glucose concentration in vitro. Metabolic and enzymatic markers of MG and glucose control were quantified and related changes in the cytoplasmic proteome and cell function—binding to collagen-I, assessed. Reversal of PDLF dysfunction by tRES-HESP was explored.ResultsIn high glucose concentration cultures, there was a ca. twofold increase in cellular MG, cellular protein MG-H1 content and decreased attachment of PDLFs to collagen-I. This was driven by increased hexokinase-2 linked glucose metabolism and related increased MG formation. Proteomics analysis revealed increased abundance of chaperonins, heat shock proteins (HSPs), Golgi-to-endoplasmic reticulum transport and ubiquitin E3 ligases involved in misfolded protein degradation in high glucose concentration, consistent with activation of the unfolded protein response by increased misfolded MG-modified proteins. PDLF dysfunction was corrected by tRES-HESP.ConclusionsIncreased hexokinase-2 linked glucose metabolism produces dicarbonyl stress, increased MG-modified protein, activation of the unfolded protein response and functional impairment of PDLFs in high glucose concentration. tRES-HESP resolves this at source by correcting increased glucose metabolism and may be of benefit in prevention of diabetic periodontal disease.


1991 ◽  
Vol 5 (2-3) ◽  
pp. 118-120 ◽  
Author(s):  
Shigehiro Katayama ◽  
Mari Abe ◽  
Kiyoshi Tanaka ◽  
Akira Omoto ◽  
Kiyohiko Negishi ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Gericke ◽  
K. Suminska-Jasińska ◽  
A. Bręborowicz

AbstractChronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) β-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (− 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.


2006 ◽  
Vol 74 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Hyun Sook Kim ◽  
Jin Woo Park ◽  
Shin Il Yeo ◽  
Byung Ju Choi ◽  
Jo Young Suh

2011 ◽  
Vol 14 (2) ◽  
pp. 32-35 ◽  
Author(s):  
Zhanna Alekseevna Akopyan ◽  
Georgy Vladimirovich Sharonov ◽  
Tatiana Nikolaevna Kochegura ◽  
Natalya Fedorovna Il'yashenko ◽  
Igor Eduardovich Belyanko ◽  
...  

Adipose issue is a source of mesenchymal stem cells (MSC) that can be used to stimulate blood vessel growth in ischemic tissues. Various metabolicdisorders including hypeglycemia may have negative effect on therapeutic properties of these cells. Aim. To study the influence of high glucose concentration on functional activity in human adipose tissue. Materials and methods. Flow cytometry and real time PCR were used to study functional activity of cultured MSC from human adipose issue at highglucose concentration. Results. Prolonged (10-12 days) incubation at a high glucose concentration (25 mM) suppressed the ability of MSC to stimulate angiogenesis. Also,glucose modified expression of genes activating and inhibiting angiogenesis but had no effect on MSC proliferation and apoptosis. Conclusion. High glucose concentration suppresses angiogenic activity of MSC in adipose tissue; it may account for incomplete restoration of bloodflow in diabetic patients.


PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134852 ◽  
Author(s):  
Chi-Yu Hsu ◽  
Jwu-Ching Shu ◽  
Mei-Hui Lin ◽  
Kowit-Yu Chong ◽  
Chien-Cheng Chen ◽  
...  

2007 ◽  
Vol 23 (1) ◽  
pp. 63-74 ◽  
Author(s):  
Mattias Gäreskog ◽  
Jonas Cederberg ◽  
Ulf J. Eriksson ◽  
Parri Wentzel

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